Radiotherapy for men diagnosed with metastatic prostate cancer

[Wendy_Winnall]

Men who are diagnosed with prostate cancer that has already spread are usually treated with hormone therapy and chemotherapy. Treatment of the tumour at the prostate site is uncommon. But recent evidence indicates that treating the prostate tumour can be helpful. A new study has demonstrated that treating the prostate tumour with radiotherapy can improve survival times, but only for men whose tumours have not spread too far.

Treatment of men diagnosed with metastatic prostate cancer.

For some men, diagnosis with prostate cancer happens after the cancer has spread to sites far away from the prostate gland. This is called metastatic prostate cancer (stage 4). Prostate cancers are capable of spreading to sites such as the lymph nodes, bones, liver and lungs. The journey is very difficult for these men, as their treatments have many side effects and are unlikely to cure them.

In the past, men who are diagnosed with metastatic prostate cancer usually received treatments such as long-term hormone therapy (androgen deprivation therapy (ADT)) and chemotherapy. Surgery and radiotherapy to remove the prostate was considered to make no difference to the cancer, but only add more side effects to cope with. Recent evidence indicates that treating the original tumour in the prostate may be more useful than was first thought.

Data from studies that look at past medical records indicate radiotherapy might be improving survival times for these men. One randomised controlled trial has been conducted with 432 men. The results from this trial (called HORRAD) showed no overall increase in survival when radiotherapy was used. However, data from the HORRAD trial indicated a possible benefit for men whose cancer has spread less. In the HORRAD trial, men who had 5 or fewer bone tumours seemed to benefit from the radiotherapy. But this trial was too small and had too few men with low spread to be certain of any difference. A larger trial was needed to answer this question.

The STAMPEDE trials for men with advanced prostate cancer

This latest study is part of a larger group of clinical trials known as STAMPEDE. This stands for Systemic Therapy for Advanced or Metastatic Prostate Cancer. The STAMPEDE trial has a new type of study design, known as multi-arm multi-stage. Standard clinical trials usually test one new treatment compared to a control group of people who have the current best treatment. A multi-arm, multi-stage trial tests several new treatment regimens simultaneously, compared to one control group.

The STAMPEDE trial group is the largest randomised clinical trial for the treatment of men with prostate cancer. It has enrolled the 10,000^th patient this year. An earlier successful study from this trial demonstrated increased survival time by using docetaxel chemotherapy and abiraterone for men starting long-term hormone therapy.

Radiotherapy for men with newly-diagnosed metastatic prostate cancer

This recent study was performed by a large team led by Dr Christopher Parker from the Royal Marsden Hospital and Institute of Cancer Research in London. Results were published in The Lancet, a top medical journal. Men with newly-diagnosed metastatic prostate cancer volunteered to take part in the trial. They were recruited through 117 hospitals in Switzerland and the UK. Volunteers were randomly allocated to the control group (usual treatment) or usual treatment plus radiotherapy to the prostate. 1032 men were allocated to the radiotherapy group and 1029 to the control group. These men were an average age of 68 and had an average PSA level of 97 ng/ml at diagnosis.

The usual treatment for men with newly-diagnosed metastatic prostate cancer is long-term hormone therapy (androgen deprivation therapy (ADT)) plus chemotherapy when necessary. 18% of these men had chemotherapy in addition to their ADT. The men in the radiotherapy group also received external beam radiotherapy (EBRT) to the prostate. They could choose either a dose per week over 6 weeks, or a dose per day for 4 weeks. The researchers then followed-up with patients over the next 5 years, to compare side effects between the two groups, as well as how well the treatments worked. The current results are from an average of 3 years follow-up.

When the control group and radiotherapy treatment group were compared, there was little difference between overall survival rates. 62% of men in the control group survived for at least 3 years, compared to 65% of men in the radiotherapy group. But this difference was not considered statistically significant. On the other hand, treatment with radiotherapy did reduce the rate of men experiencing disease progression. This means that the rate of men undergoing disease progression (defined as PSA rise, or new tumours seen on scans, or death from prostate cancer) was lower for those who had radiotherapy.

The researchers then looked at survival rates for different groups of men. They found that men with low disease spread had significantly better survival rates if they had radiotherapy added to their usual treatment. 81% of men with low disease spread survival at least 3 years if they had radiotherapy, compared to 73% of men with low spread who didn’t have radiotherapy. This benefit of radiotherapy was not seen for men who had a higher disease spread.

In this study, men with high disease spread were defined as having 4 or more bone tumours and one or more outside the spine or pelvis, and/or they had metastatic tumours in other regions than their bones. Men whose cancer didn’t meet these criteria were considered to have low metastatic spread.

The men having radiotherapy were able to cope with the treatment quite well. 5% of men having radiotherapy reported problems associated with the radiotherapy during the treatment, and 4% reported problems after treatment. The rate men reporting at least one severe problem in the radiotherapy group was very similar to the control group.

The STAMPEDE researchers have produced this useful short video for patients explaining the main results and how their trial was conducted.

Due to the results of this trial, the researchers believe that radiotherapy should now become a standard treatment for men newly-diagnosed with metastatic prostate cancer, so long as it has not spread too far. This is great news for patients, as unlike a new drug, radiotherapy is already available and affordable in many other countries.